Prostate cancers that are resistant to androgen deprivation therapy are more invasive and more likely to spread to other organs than androgen dependent prostate cancers, UCLA cancer researchers have found.
Virtually all prostate cancers are androgen dependent at first, but they progress and become resistant over time. These hormone refractory or castration resistant cancers can grow despite surgical or medical therapies that deplete testosterone.
The UCLA study is the first to link that progression with the cancer's tendency to spread to other organs. The findings could change the way some prostate cancers are treated, spurring earlier use of hormone therapy to prevent the cancer's spread, said Dr. Robert Reiter, a professor of urology, a researcher at UCLA's Jonsson Cancer Center and senior author of the study.
Published in the Feb. 15 issue of the journal Cancer Research, the study makes the connection between androgen receptor and the spread of prostate cancer as well as the progression to androgen independence. Previous studies have shown that the androgen receptor is responsible for the growth of hormone refractory prostate cancer. However, no one has associated the spread of prostate cancer to the androgen receptor, Reiter said.
“We started noticing that the castration resistant prostate cancer models in the lab seemed to express genes that are typically associated with the spread of cancer,” Reiter said. “We began to ask what cell signaling pathways might be responsible. We looked at the androgen receptor and were surprised to find that it was not only overexpressed in castration resistant cancers but also in invasive cancers that still relied on androgen to grow.”
The study found that overexpression of the androgen receptor was critical to the cancer becoming more invasive. If a therapy could be found that blocked overexpression of the receptor, it might prevent the spread of certain prostate cancers.
Traditionally, doctors don't like to use hormone treatment – which stops the production of testosterone - early on in the treatment of prostate cancer because of the harsh side effects, which can include hot flashes, osteoporosis and sexual dysfunction. In the past, doctors have waited until the cancer spread to prescribe hormone therapy, Reiter said.